Are nicotinoids protonated on the pyridine or the amino nitrogen in the gas phase?

The gas-phase basicities (GBs) of 12 nicotinoids were calculated for the two potential sites of protonation, the sp(2) pyridine and the sp(3) amino nitrogen atoms, at the B3LYP/6-311 + G(3df,2p)//B3LYP/6-31G(d,p) level and estimated from substituent effects on the GBs of 2-substituted pyrrolidines and N-methylpyrrolidines. It was found that, in contrast to the Nsp(3) protonation in water, nicotinoids with a secondary amino nitrogen (substituted nornicotines, anabasine, anatabine) are protonated on the pyridine nitrogen. Nicotinoids with a tertiary amino nitrogen (substituted nicotines, N-methylanabasine, N-methylanatabine) are protonated on either the pyridine or the amino nitrogen, depending on the electronic effects of the substituents and the strength of an intramolecular CH center dot center dot center dot Nsp(3) hydrogen bond. Copyright (c) 2005 John Wiley & Sons, Ltd.